A Study of MabThera (Rituximab) Plus Chlorambucil in Patients With Previously Untreated Chronic Lymphocytic Leukemia.
2017년 7월 6일 업데이트: Hoffmann-La Roche
A Study of Chlorambucil Plus MabThera as Induction Therapy Followed in Responders by Maintenance Therapy Versus Observation on Response Rate in Patients >=60 Years With Previously Untreated Chronic Lymphocytic Leukemia
This single arm study will assess the efficacy and safety of MabThera + chlorambucil as induction therapy, followed in responders by maintenance therapy or observation in elderly patients with previously untreated chronic lymphocytic leukemia.
During the induction phase patients will receive 2 x 4 weekly courses of chlorambucil followed by 8 x 4 weekly courses of chlorambucil + MabThera.
Subsequently, responders will be randomized to receive 12 doses of MabThera given every 8 weeks, or no further treatment.
The anticipated time on study treatment is 2+ years, and the target sample size is <100 individuals.
연구 개요
연구 유형
중재적
등록 (실제)
97
단계
- 2 단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Calabria
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Catanzaro, Calabria, 이탈리아, 88100
- Az. Osp. Pugliese; Dh Oncologico
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Cosenza, Calabria, 이탈리아, 87100
- P.O. Annunziata; U.O. Ematologia
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Reggio Calabria, Calabria, 이탈리아, 89100
- Ospedale Riuniti; Divisione Di Ematologia
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Campania
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Napoli, Campania, 이탈리아, 80131
- Ospedale Cardarelli; Divisione Di Ematologia
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Emilia-Romagna
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Bologna, Emilia-Romagna, 이탈리아, 40138
- A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna
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Ferrara, Emilia-Romagna, 이탈리아, 44100
- Arcispedale S. Anna; Sezione Di Ematologia
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Lazio
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Roma, Lazio, 이탈리아, 00161
- Universita' Degli Studi La Sapienza-Ist.Di Ematologia;Dip. Biotecnologie Cel CELLULARI ED EMATOLOGIA
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Roma, Lazio, 이탈리아, 00144
- Ospedale S. Eugenio; Divisione Di Ematologia
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Liguria
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Genova, Liguria, 이탈리아, 16132
- Uni Degli Studi Di Genova; 1A Divisione Di Ematologia
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Lombardia
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Milano, Lombardia, 이탈리아, 20122
- Ospedale Maggiore Di Milano; U.O. Ematologia I - Padiglione Marcora
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Milano, Lombardia, 이탈리아, 20162
- Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia
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Piemonte
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Torino, Piemonte, 이탈리아, 10126
- A.O.U. Citta' Della Salute E Della Scienza-P.O. Molinette;S.C. Ematologia
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Torino, Piemonte, 이탈리아, 10126
- Ospedale Molinette - Universita' Di Torino; Cliniche Universitarie Ematologia I
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Puglia
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Bari, Puglia, 이탈리아, 70124
- Uni Degli Studi Di Bari, Policlinico; Cattedra Di Ematologia,Dipart. Di Medicina Interna E Publica
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Sicilia
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Messina, Sicilia, 이탈리아, 98165
- Az. Osp. Papardo; Struttura Complessa Di Ematologia
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Via S. Sofia 78, Sicilia, 이탈리아, 95123
- Ospedale Ferrarotto; Divisione Di Ematologia
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Toscana
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Firenze, Toscana, 이탈리아, 50135
- Az. Osp. Di Careggi; Divisione Di Ematologia
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Siena, Toscana, 이탈리아, 53100
- A.O. Universitaria Senese; Ematologia
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Veneto
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Padova, Veneto, 이탈리아, 35128
- Uni Degli Studi; Dip.Med.Clinica E Sperim. Ematologia
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Verona, Veneto, 이탈리아, 37134
- Policlinico G. B. Rossi; Divisione Di Ematologia
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
60년 이상 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
Inclusion Criteria:
- adult patients, >=60 years of age;
- CD20+ chronic lymphocytic leukemia (CLL);
- no previous treatment for CLL;
- ECOG performance status 0-1.
Exclusion Criteria:
- co-morbid conditions requiring long term use of systemic corticosteroids during study treatment;
- history of severe cardiac disease;
- transformation to aggressive B-cell malignancy.
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: 1
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375mg/m2 iv on day 1 of course 3; 500mg/m2 iv on day 1 of courses 4-8 (induction phase); 375mg/m2 iv every 8 weeks (maintenance phase).
8mg/m2 po on days 1-7 of courses 1-8
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Percentage of Participants With Documented CR, CRi, or PR at the End of Induction Treatment
기간: Month 10
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CR defined as: 1) laboratory CR: peripheral blood lymphocytes (PBL) less than (<) 4000/microliter (μL), neutrophils (PMN) greater than (>) 1500/μL, platelets >100,000/μL, and hemoglobin (Hb) >11 grams per deciliter (g/dL); 2) clinical CR: lymph nodes (LN) <1.5 centimeter (cm), and no constitutional symptoms, hepatomegaly (HM) or splenomegaly (SM); 3) instrumental CR: LN <1.5 cm and no HM/SM, and 4) bone marrow (BM) CR: normocellular aspirate/biopsy for participant age <30 percent (%) lymphocytes, and no B cell lymphoid nodules.
CRi was defined as CR with anemia, thrombocytopenia, or neutropenia not related to chronic lymphocytic leukemia (CLL), with no clonal infiltrate in aspirate or biopsy.
PR defined as: a 50% decrease in PBL, a 50% decrease in LN size, no increase in LN size, no new enlarged LN, a 50% reduction from baseline (BL) in the HM/SM, and 1 of the following: PMN >1500/μL, platelets >100,000/μL or >50% improvement from BL, and Hb >11.0 g/dL or >50% improvement from BL.
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Month 10
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Percentage of Participants With Documented CR, CRi, or PR at the End of Study
기간: Month 35
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CR defined as: 1) laboratory CR: PBL <4000/μL, PMN > 1500/μL, platelets > 100,000/μL, and Hb > 11 g/dL; 2) clinical CR: LN < 1.5 cm, and no constitutional symptoms, HM or SM; 3) instrumental CR: LN < 1.5 cm and no HM/SM, and 4) bone marrow CR: normocellular aspirate/biopsy for participant age < 30% lymphocytes, and no B cell lymphoid nodules.
CRi was defined as CR with anemia, thrombocytopenia, or neutropenia not related to CLL, with no clonal infiltrate in aspirate or biopsy.
PR defined as: a 50% decrease in PBL, a 50% decrease in LN size, no increase in LN size, no new enlarged LN, a 50% reduction from BL in the HM/SM, and 1 of the following: PMN > 1500/μL, platelets > 100,000/μL or > 50% improvement from BL, and Hb >11.0 g/dL or > 50% improvement from BL.
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Month 35
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Percentage of Participants With CR, CRi, PR, Stable Disease (SD), Progressive Disease (PD), Relapse, or Nodular PR at the End of Induction Treatment
기간: Month 10
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CR, CRi, and PR as previously defined.
PD was defined by 1 of the following: 1) lymphadenopathy: any new lesion, HM/SM, or other organ infiltrates, or a greater than or equal to (≥) 50% increase in greatest diameter of any previously noted lesion; 2) a ≥ 50% increase in previously noted HM/SM, or new appearance of HM/SM; 3) a ≥ 50% increase in blood lymphocyte count with at least 5000 B lymphocytes/μL; 4) transformation to a more aggressive histology, e.g., Richter's syndrome; or 5) occurrence of cytopenia attributable to CLL.
SD was defined by the absence of necessary criteria to achieve CR or PR, but no advancement to PD. Relapse was defined by a previously noted CR or PR with advancement to PD after a period of ≥ 6 months.
Nodular PR was defined by the presence of residual lymphoid nodules.
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Month 10
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Percentage of Participants With CR, PR, SD, PD, Relapse, or Nodular PR at the End of Study
기간: Month 35
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CR, and PR as previously defined.
PD was defined by 1 of the following: 1) lymphadenopathy: any new lesion, HM/SM, or other organ infiltrates, or a ≥ 50% increase in greatest diameter of any previously noted lesion; 2) a ≥50% increase in previously noted HM/SM, or new appearance of HM/SM; 3) a ≥50% increase in blood lymphocyte count with at least 5000 B lymphocytes/μL; 4) transformation to a more aggressive histology, e.g., Richter's syndrome; or 5) occurrence of cytopenia attributable to CLL.
SD was defined by the absence of necessary criteria to achieve CR or PR, but no advancement to PD. Relapse was defined by a previously noted CR or PR with advancement to PD after a period of ≥6 months.
Nodular PR was defined by the presence of residual lymphoid nodules.
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Month 35
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Number of Participants With Immunophenotypic CR - BM, Immunophenotypic CR - Peripheral Blood (PB), Molecular CR - BM, or Molecular CR - PB at the End of Induction Treatment
기간: Month 10
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Immunophenotypic CR was defined as the absence of minimal residual disease (MRD) evaluated in participants with CR by 4-color flow cytometry of PB and BM B cells to confirm that tissue was comprised of non-CLL cells.
Molecular CR was defined as the absence of MRD evaluated in participants with CR by quantitative polymerase chain reaction (PCR) in PB and BM B cells to confirm that tissue was comprised of non-CLL cells.
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Month 10
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Percentage of Participants With CR, CRi, PR, SD, PD, or Relapse at the End of Study
기간: Month 35
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CR, CRi, PR, SD, PD, relapse, and nodular PR as previously defined.
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Month 35
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Percentage of Participants With Immunophenotypic CR - BM or Immunophenotypic CR - PB at the End of Study
기간: Month 35
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Immunophenotypic CR was defined as the absence of MRD evaluated in participants who achieved CR by 4-color flow cytometry of PB and BM B cells to confirm that tissue was comprised of non-CLL cells.
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Month 35
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Percentage of Participants With Molecular CR - BM or Molecular CR - PB at the End of Study
기간: Month 35
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Molecular CR was defined as the absence of MRD evaluated in participants who achieved CR by quantitative PCR in PB and BM B cells to confirm that tissue was comprised of non-CLL cells.
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Month 35
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Number of Participants With Disease Progression, Relapse, Death, Withdrawal Because of an Adverse Event (AE), or New CLL Treatment
기간: Screening, Days 1 and 15 of Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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Event-free Survival (EFS) was defined as the time from the first dose of study treatment to the date of first documentation of disease progression, relapse for participants with previous CR, death due to any cause, withdrawal due to AE, or beginning new CLL treatment.
CR and PD as previously defined.
Participants were censored at the time of data cut-off to the most recent date of disease assessment.
Participants without a post-BL disease assessment were censored at the time of first dose of study treatment.
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Screening, Days 1 and 15 of Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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EFS
기간: Screening, Days 1 and 15 of Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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The median time, in days, from the the date of first dose of study treatment to the date of first documentation of disease progression, relapse for participants with CR, death due to any cause, withdrawal due to AE, or new CLL treatment.
CR and PD as previously defined.
Participants were censored at the time of data cut-off to the most recent date of disease assessment.
Participants without a post-BL disease assessment were censored at the time of first dose if study treatment.
The 95% CI was determined using Kaplan-Meier methodology.
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Screening, Days 1 and 15 of Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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Number of Participants With Disease Progression or Death
기간: Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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Progression-free survival (PFS) was defined as the time from the first dose of study treatment to the first documentation of disease progression or death.
PD as previously defined.
Participants who were withdrawn from the study without documented disease progression were censored at the date of the last tumor assessment when the participant was known to be progression-free.
Participants without a post-BL tumor assessment, but known to be alive, were censored at the time of the first dose of study treatment.
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Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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PFS
기간: Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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The median time, in days, from the date of the first dose of study treatment to the date of first documentation of disease progression or death.
CR and PD as previously defined.
Participants who were withdrawn from the study without documented disease progression were censored at the date of the last tumor assessment when the participant was known to be progression-free.
Participants without a post-BL tumor assessment, but known to be alive, were censored at the time of the first dose of study treatment.
The 95% CI was determined using Kaplan-Meier methodology.
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Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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Number of Participants With New CLL Treatment or Death
기간: Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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Time to new CLL treatment (TTNT) was defined as the time from the first dose of study treatment to the date of new CLL treatment received or the date of death from any cause.
Participants who did not receive new CLL treatment and were alive at the time of the analysis were censored at the date of the last follow-up assessment.
Participants without a follow-up assessment were censored at the day of last dose of study treatment.
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Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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Time to Next Treatment (TTNT)
기간: Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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The mean time, in days, from the date of the first dose of study treatment to the date of new CLL treatment or the date of death from any cause.
Participants who did not receive new CLL treatment and were alive at the time of the analysis were censored at the date of the last follow-up assessment.
Participants without a follow-up assessment were censored at the day of last dose of study treatment.
Mean survival time and it's standard error (SE) were underestimated because the largest observation was censored and the estimation was restricted to the largest event time.
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Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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Number of Participants Who Died
기간: Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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Overall Survival (OS) was defined as the time from the date of the first dose of study treatment to the date of death due to any cause.
Participants were censored at the date of the last follow-up assessment.
Participants without a follow-up assessment were censored at the day of last dose of study treatment.
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Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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OS
기간: Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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The mean time, in days, from the date of the first dose of study treatment to the date of death due to any cause.
Participants were censored at the date of the last follow-up assessment.
Participants without a follow-up assessment were censored at the day of last dose of study treatment.
The mean survival time and it's SE were underestimated because the largest observation was censored and the estimation was restricted to the largest event time.
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Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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Number of Participants With PD or Death After a Confirmed CR, CRi, or PR
기간: Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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Duration of response was defined as the time from the date of the first documented CR, CRi, or PR to the date of disease progression or death.
CR, CRi, PR, and PD as previously defined.
Participants with no documented PD after CR, CRi, or PR were censored at the last date at which they were known to have had CR, CRi, or PR, respectively.
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Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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Duration of Response
기간: Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
|
The mean time, in days, from the date of first documented CR, CRi or PR to the date disease progression or death.
CR, CRi, PR, and PD as previously defined.
Participants with no documented PD after CR, CRi, or PR were censored at the last date at which they were known to have had CR, CRi, or PR, respectively.
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Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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Number of Participants With PD or Death After a Confirmed CR/CRi
기간: Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
|
Disease-free survival was defined at the time from the date of first documented CR or CRi to the date of disease progression or death.
CR, CRi, and PD as previously defined.
Participants with no documented PD after CR or CRi were censored on the last date at which they were known to have had CR or CRi.
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Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
|
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Disease-Free Survival
기간: Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
|
The mean time, in days, from the date of first documented CR or CRi to the date of disease progression or death.
CR, CRi, and PD as previously defined.
Participants with no documented PD after CR or CRi were censored on the last date at which they were known to have had CR or CRi.
In both groups, the mean survival time and its standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time.
|
Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.
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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
2008년 11월 3일
기본 완료 (실제)
2013년 1월 14일
연구 완료 (실제)
2013년 1월 14일
연구 등록 날짜
최초 제출
2008년 8월 18일
QC 기준을 충족하는 최초 제출
2008년 8월 19일
처음 게시됨 (추정)
2008년 8월 20일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2017년 8월 15일
QC 기준을 충족하는 마지막 업데이트 제출
2017년 7월 6일
마지막으로 확인됨
2017년 6월 1일
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- ML21445
- 2008-001612-20
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .